The major histocompatibility complex (MHC) class I genes encode cell surface glycoproteins which play an important role in the generation and specificity of immune responses to pathogens and tumor cells. The importance of MHC class I molecules in immune protection is illustrated by the inability of animals to mounteffective immune responses to cells expressing reduced levels of class I proteins. Reduced class I expression may be one mechanism by which some virus-infected and transformed cells escape immune detection to cause disease. Therefore, an understanding of the mechanisms by which class I gene expression is regulated in normal cells, and the mechanisms by which virus infection or transformation alters class I expression, may lead to the development of treatment methods, which enhance the ability of an animal to eliminate such abnormalcells. The longterm objective of this project is to determine the molecular mechanisms by which expression of MHC class I genes is regulated. This regulation appears to be very complex. The proposed studies will utilize a modelsystem that may be relatively limited in complexity, namely, a panel of retrovirus-induced tumor cell lines that are very similar except for their constitutive and inducible levels of class I expression. The initial experiments proposed are designed to determine the level at which constitutive classI expression is inhibited in one of these cell lines. Previous experiments have indicated that this regulation was at the level of steady stateclass I RNA levels. The proposed experiments will: (1) determine whether the inhibition of class I expression is at the level of transcription or post-transcriptional events; (2) examine the role of cis-acting versus trans-acting regulatory elements by transfecting intact class I genes into the classI negative cells; and (3) identify and characterize any such regulatory elementsindicated. The results of these experiments then may be used to investigate the more complicated regulation of inducible class I gene expression, as well as the mechanism of inhibition of class I expression in othercell lines.